Salivary glycoproteins, the major constituent of saliva, play important roles in the protection of soft oral tissue and teeth from ulcerations, abrasions and caries. This task is accomplished when glycoprotein is sufficiently acylated thus capable to form complexes with lipids and proteins of saliva to adhere to oral surfaces and to repel proteolytic attacks of hostile environments. According to our recent reports, the covalently linked fatty acyl residues are added to the protein core of glycoproteins during co-post translational modifications and that the acylating enzyme responsible for the addition of these fatty acyl residues, is a rough endoplasmic reticulum (RER) origin, having its catalytic site exposed to the cytosolic side of RER. However, the understanding of the enzyme protein fatty acylesterase (PFAE) responsible for the removal of the fatty acyl residues, which may alter the net content of fatty acyl residues present in glycoproteins and which may modify its function and its susceptibility to protease, is very limited. Variations in the content of covalently linked fatty acids found in the salivary glycoproteins of caries resistant and susceptible individual provide indirect evidence suggesting that the acylesterase may be involved in modulation of secretory proteins and its altered activity is evident in pathological conditions with symptoms of scanty but precipitously thick saliva. Thus the present project is directed to explore the presence of PFAE in saliva and in salivary glands. The approach to the project is to identify the subcellular fraction of a salivary cell having maximal PFAE activity and to rule out the possibilities that PFAE activity is different than protein fatty acyltransferase and Lipid Lipases. Then our aim is to determine the topology of PFAE in RER using mild trypsinization of RER. The findings from this project should improve our understanding of the synthesis and processing of acylated proteins and should lead to the study on the regulation of PFAE activity under pathological conditions.